Les recherches récentes ont cherché à appréhender la contribution de la théorie de l'esprit – appréhension du monde mental en termes d'états mentaux – au développement de la métacognition – connaissances sur le fonctionnement cognitif. C'est dans ce contexte que nous avons réalisé une étude longitudinale auprès d'enfants français scolarisés et âgés de 4 ans au premier temps. Les enfants (N=31) ont été rencontrés tous les 4 mois pendant deux années scolaires – moyenne et grande section de maternelle. L'objectif de notre étude était d'appréhender le développement de la métamémoire déclarative au cours de la période préscolaire, mais également celui de trois de ces précurseurs cognitifs – théorie de l'esprit, langage et mémoire épisodique. Les analyses de régression linéaire multiple nous ont permis d'appréhender les liens développementaux entre ces compétences, mais également de déterminer la contribution de chacun de ces trois précurseurs au développement de la métamémoire déclarative. Les résultats soulignent l'importance de distinguer soi/autrui dans l'évaluation des compétences et confirment que la théorie de l'esprit a un impact dans le développement de la métamémoire, principalement pour la compréhension de l'influence du nombre sur la mémorisation. / Until recently, two different kinds of research have been separately conducted on knowledge about mental world: those on metacognition that have studied knowledge about cognition and research on theory-of-mind, which refers to knowledge about mental states. A novel perspective of research tends to study the link between metacognition and theory-of-mind developments. The assumption is that theory-of-mind is a cognitive tool for understanding the cognitive functioning – i.e. metacognition. In this framework, we conducted a longitudinal study to investigate the developmental relationships between a special kind of metacognition – metamemory which is knowledge about memory functioning – and theory-of-mind, and the contribution of some cognitive precursors on declarative metamemory – language and episodic memory. Thirty-one children were recruited and evaluated on these four competencies every four months during two school years. Multiple regression analyses conducted on metamemory scores confirmed that theory-of-mind competences play a role in the declarative metamemory emergence.

<p>Neuroimaging studies of episodic memory, or memory of events from our personal past, have predominantly focused their attention on medial temporal lobe (MTL). There is growing acknowledgement however, from the cognitive neuroscience of memory literature, that regions outside the MTL can support episodic memory processes. The medial prefrontal cortex is one such region garnering increasing interest from researchers. Using behavioral and functional magnetic resonance imaging measures, over two studies, this thesis provides evidence of a mnemonic role of the medial PFC. In the first study, participants were scanned while judging the extent to which they agreed or disagreed with the sociopolitical views of unfamiliar individuals. Behavioral tests of associative recognition revealed that participants remembered with high confidence viewpoints previously linked with judgments of strong agreement/disagreement. Neurally, the medial PFC mediated the interaction between high-confidence associative recognition memory and beliefs associated with strong agree/disagree judgments. In an effort to generalize this finding to well-established associative information, in the second study, we investigated associative recognition memory for real-world concepts. Object-scene pairs congruent or incongruent with a preexisting schema were presented to participants in a cued-recall paradigm. Behavioral tests of conceptual and perceptual recognition revealed memory enhancements arising from strong resonance between presented pairs and preexisting schemas. Neurally, the medial PFC tracked increases in visual recall of schema-congruent pairs whereas the MTL tracked increases in visual recall of schema-incongruent pairs. Additionally, ventral areas of the medial PFC tracked conceptual components of visual recall specifically for schema-congruent pairs. These findings are consistent with a recent theoretical proposal of medial PFC contributions to memory for schema-related content. Collectively, these studies provide evidence of a role for the medial PFC in associative recognition memory persisting for associative information deployed in our daily social interactions and for those associations formed over multiple learning episodes. Additionally, this set of findings advance our understanding of the cognitive contributions of the medial PFC beyond its canonical role in processes underlying social cognition.</p> / Dissertation

Thesis advisor: Scott D. Slotnick / Episodic memory is a constructive process in which a system of sensory and control processes works to transport one’s conscious mind through time–in essence, recreating a previous perceptual experience. For instance, sensory-specific activity that was associated with an original encoding experience is reinstated during retrieval–almost as if the sensory regions are processing the stimulus again, albeit this activation is smaller in spatial extent. This process of sensory-specific reinstatement occurs across all sensory modalities (e.g., Gottfried et al., 2004; Nyberg et al., 2001; Vaidya et al., 2002; Wheeler et al., 2000). That is, retrieval of a visually encoded stimulus (e.g., a picture of a dog) reinstates activity in the visual cortex, while retrieval of an aurally encoded stimulus (e.g., a barking dog) reinstates activity in the auditory cortex. In Chapter 1 and Chapter 2, I demonstrate the specificity of such sensory reinstatement during true memory for visual features and investigate the role of such sensory regions during the construction of false memory for visual features. In addition to sensory processes, our conscious experience of memory also relies on control regions. At the center of this memory control network sits a key memory structure, the hippocampus, as well as other important control regions such as the dorsolateral prefrontal cortex and the parietal cortex. Furthermore, the parahippocampal cortex appears to play a critical role in memory; however, the exact role of this region has been debated (Aminoff, Kverga, & Bar, 2013). In Chapter 3, I investigate the functional role of the parahippocampal cortex during true memory and false memory, and provide evidence that the parahippocampal cortex mediates general contextual processing.

Activation in the hippocampus (HC) and prefrontal cortex (PFC) is critical to accurately retrieve overlapping sequences. Experiments 1 and 2 tested the hypotheses that activation in and interaction between HC and PFC increases as overlap between sequences increases in a non-spatial task. Experiment 3 tested the hypothesis that theta oscillations are involved in orchestrating interactions between HC and PFC in a spatial task with overlapping elements. In the first two studies, 17 participants (aged 18-34; 11 female) learned sequences consisting of a picture frame, face, and scene. Conditions varied by degree of overlap. Using fMRI, Experiment 1 tested how degree of overlap affected HC and PFC activation. In overlapping sequences, middle and posterior HC were active when predictability of the correct response increased, dorsolateral PFC was active when participants were able to ascertain the correct set of sequences, and ventrolateral PFC was active when inhibition of interfering associations was required. Experiment 2 examined functional connectivity of HC and PFC during disambiguation. Low- and high-overlap conditions were associated with increased connectivity in separate regions at different times indicating that retrieval under the two conditions used different neural networks and strategies. Low-overlap trials were associated with increased connectivity between HC and prefrontal and parietal regions. High-overlap trials showed increased connectivity between lateral PFC and visual areas, indicating that imagery may be necessary for accurate performance. Using EEG recording, Experiment 3 examined theta activity during retrieval of well-learned, overlapping and non-overlapping mazes in 17 participants (aged 18-34, 11 female). Theta activity increased in overlapping mazes during the first of four hallways, suggesting participants were looking ahead to upcoming turns in the maze. Theta activity increased at the beginning and choice point of the third overlapping hallway, possibly in response to interference from the paired, overlapping maze. These studies provide evidence that (1) overlapping associations in non-spatial sequences elicit interactions between hippocampus and lateral prefrontal cortex, (2) increasing the degree of overlap changes the neural processes required to perform the task, and (3) theta power increases in response to increased cognitive demand and maintenance of sequence information needed to differentiate between overlapping spatial routes.

La neurogenèse adulte du gyrus denté de l’hippocampe joue un rôle essentiel dans les processus mnésiques dépendants de l’hippocampe, mais son rôle dans des formes complexes de mémoire comme la mémoire épisodique n’a jamais été exploré. Le travail de cette thèse porte sur l’étude de l’implication des nouveaux neurones de l’hippocampe dans la mise en mémoire d’un souvenir épisodique à long terme. Nous avons développé une nouvelle tâche de mémoire épisodique reposant sur la présentation occasionnelle d’épisodes permettant d’encoder des informations de type « Quoi – Où – Dans quel contexte ». Nous montrons pour la première fois que les rats sont capables de se souvenir à très long terme de brefs épisodes de vie et d’utiliser cette mémoire d’une manière flexible. La caractérisation des profils de rétention permet d’accéder aux capacités individuelles de recollection des différents éléments du souvenir et montre que le rappel fiable de la mémoire épisodique nécessite l’intégrité de l’hippocampe et met en jeu un vaste réseau hippocampo-cortical dont l’activation est corrélée au rappel. Les performances de rats soumis à une irradiation focale de l’hippocampe montrent que la neurogenèse adulte hippocampique contribue de façon significative à la consolidation et au rappel fiable du souvenir épisodique. Ces résultats sont discutés dans le cadre d’une implication de la neurogenèse adulte dans la résolution de la mise en mémoire d’événements occasionnels dans le but de discriminer deux épisodes de vie proches, en lien avec les fonctions de séparation et de complétion de patterns de l’hippocampe. Par ailleurs, les mécanismes moléculaires qui sous-tendent le recrutement des nouveaux neurones lors d’un apprentissage restent inconnus. Nous avons analysé le rôle du gène immédiat précoce Zif268, acteur moléculaire essentiel dans les processus mnésiques, et montrons que ce gène joue un rôle crucial dans la sélection et le recrutement des nouveaux neurones lors de la mémorisation au cours de leur période critique d’intégration dans les réseaux neuronaux de l’hippocampe. Ce travail apporte des éléments nouveaux sur la participation des nouveaux neurones hippocampiques dans les processus mnésiques dans une situation à forte demande cognitive basée sur l’encodage d’une représentation intégrée et résolue d’événements occasionnels complexes, ainsi que sur les mécanismes qui sous-tendent leur recrutement. / Adult hippocampal neurogenesis plays a critical role in hippocampal-dependent memory, however its role in complex forms of memory such as episodic memory has not as yet been explored. The work presented in this thesis focuses on the issue of the involvement of newborn hippocampal neurons in long term episodic memory. We developed a new episodic memory task based on the presentation of occasional episodes allowing rats to encode “What – Where – In which context” information. We show for the first time that rats are able to remember on the long term brief past episodes of life and to use their episodic memory in a flexible manner. The characterization of retention profiles allows us to identify individual abilities in the recollection of the various elements of the memory and shows that episodic memory recall requires the integrity of the hippocampus and involves a hippocampo-cortical network, the activation of which correlates with recall performance. Performance of rats subjected to focal irradiation of the hippocampus shows that adult hippocampal neurogenesis contributes significantly to the consolidation and faithful recall of episodic memory. These results are discussed in the context of the implication of hippocampal newborn neurons in the resolution of memories of occasional events in order to discriminate different, but closely related episodes of life in relation to pattern separation and pattern completion functions of the hippocampus. Furthermore, the molecular mechanisms underlying the recruitment of newborn hippocampal neurons by learning remain to date unknown. We investigated the role of Zif268, an immediate early gene known to play an essential role in memory processes, and show that this gene plays a crucial role in the selection and recruitment of newborn hippocampal neurons by learning during their critical period of integration in hippocampal neural networks. Overall, this work brings new knowledge on the contribution of newborn hippocampal neurons to memory processes in a highly demanding cognitive situation based on the encoding of an integrated and high-resolution representation of complex occasional events, and on the mechanisms underlying their recruitment.

Introdução: independentemente do grau de incapacidade física, o declínio cognitivo tem sido considerado motivo de maior impacto em importantes aspectos da vida diária dos pacientes com Esclerose Múltipla (EM) como o gerenciamento de tarefas domésticas, participação na sociedade e manutenção do emprego. Alterações de Memória Episódica (ME) em pacientes com EM são comumente descritas na literatura, sendo observadas em 40% a 65% dos casos. Seu impacto já é observado em pacientes com Esclerose Múltipla Remitente-Recorrente (EMRR) incipiente e pode ser um indicador de pior prognóstico para evolução da doença. Adicionalmente, déficits na memória verbal bem como na velocidade de processamento de informação e função executiva predizem condição ocupacional dos portadores da doença. Há vários trabalhos transversais na literatura científica que visam investigar sobre alterações cognitivas encontradas nestes pacientes. Entretanto, os estudos longitudinais são escassos e estes têm revelado resultados inconclusivos e divergentes. Além disso, tanto nos estudos transversais quanto nos estudos longitudinais, não há preocupação em caracterizar de forma aprofundada o declínio da Memória Episódica Verbal (MEV) especificamente. Objetivo: neste estudo, investigamos a MEV de pacientes com EMRR e sua evolução através de avaliação longitudinal. Métodos: vinte e nove pacientes com EMRR foram submetidos a duas avaliações neuropsicológicas realizadas entre um intervalo de tempo médio de 4,5 anos. Vinte e seis controles saudáveis foram submetidos à uma única e idêntica avaliação neuropsicológica. Considerou-se nível de significância p < 0,05 para delinear diferenças estatísticas entre os grupos nas análises Mann Withney e Wilcoxon pareado. Resultados: não houve diferença estatística nos resultados dos testes de MEV entre a primeira e a segunda avaliação neuropsicológica realizada pelos pacientes. Houve discrepância estatística nos resultados dos testes de MEV entre o grupo de controles e grupo de pacientes no momento da avaliação inicial. Em contrapartida, no momento da segunda avaliação o grupo de pacientes não se diferenciou estatisticamente do grupo dos controles. Conclusões: a estabilização ou discreta melhora do desempenho dos pacientes com EMRR entre a avaliação inicial e o follow-up em testes de MEV, pode estar relacionada ao fato de que neste estudo foram incluídos predominantemente jovens adultos na amostra, com a forma clínica mais branda da doença. Possível processo de neuroplasticidade cerebral, ou mesmo inclusão de casos benignos da EM precisam ser considerados. Atrelado a isso, deve-se considerar que o breve período de follow-up pode não ter sido o suficiente para detectar possíveis déficits a longo prazo / Introduction: Regardless of the degree of physical disability, cognitive decline has been considered as having the greatest impact on important aspects of the daily life of Multiple Sclerosis (MS) patients, such as managing household tasks, participation in society and maintaining employment. Changes in Episodic Memory (EM) in MS patients are commonly described in the literature and are observed in 40% to 65% of cases. Its impact is already observed in patients with incipient Relapsing-Remitting Multiple Sclerosis (RRMS) and may be an indicator of a worse prognosis for disease progression. In addition, deficits in verbal memory as well as in the speed of information processing and executive function predict the occupational condition of the patients with the disease. There are several transversal works in the scientific literature that aim to investigate cognitive alterations found in these patients. However, longitudinal studies are scarce and these have revealed inconclusive and divergent results. Moreover, in both crosssectional studies and longitudinal studies, there is no concern to characterize in depth the decline of Verbal Episodic Memory (VEM) specifically. Objective: In this study, we investigated the VEM of patients with RRMS and its evolution through longitudinal evaluation. Methods: Twenty-nine patients with RRMS were submitted to two neuropsychological evaluations performed between a mean time interval of 4.5 years. Twenty-six healthy controls were submitted to a single and identical neuropsychological evaluation. A significance level of p < 0.05 was used to delineate statistical differences between the groups in the Mann Withney and Wilcoxon paired analyzes. Results: There was no statistical difference in the VEM results between the first and second neuropsychological evaluation performed by the patients. There was a statistical discrepancy in the VEM results between the control group and the patient group at the time of the initial evaluation. In contrast, at the time of the second evaluation, the group of patients did not differ statistically from the control group. Conclusions: The stabilization or discrete improvement in the performance of RRMS patients between the initial evaluation and the follow-up in the VEM trials may be related to the fact that in this study, predominantly young adults were included in the sample, with the mildest clinical form of the disease. Possible process of cerebral neuroplasticity, or even inclusion of benign cases of MS need to be considered. Coupled with this, one should consider that the brief follow-up period may not have been enough to detect possible long-term deficits

Long-term declarative memory depends on pattern separation, which reduces the degree of overlap between similar representations, to maintain memory specificity, and on pattern completion, which occurs when a degraded cue is used to retrieve a previously stored memory. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and fMRI to focus on the hippocampus, to the exclusion of cortical processing. We aim to investigate the influences extra-hippocampal processes have on pattern separation in the following two studies. Study 1. Computational models of pattern completion suggest it occurs cortically and results in generalized memories whereas pattern separation occurs in the hippocampus and results in memory specificity. It is unknown how the incongruity of these two neuronal processes is resolved. Many studies evaluating the neuronal correlates of pattern separation have used fMRI to evaluate activity in the hippocampus. The sluggish time resolution of fMRI and the restricted spatial focus leave room for considerable differences between pattern completion and pattern separation to go undetected. Here, we use encephalography (EEG) and an event-related potential (ERP) analysis to examine neuronal activity during pattern separation and pattern completion to investigate whether or not cortical processing is employed to resolve the discrepancy between these two neuronal processes. We largely did not observe differences between the ERPs associated with pattern separation and pattern completion. Failure to identify neuronal differences could result from the bulk of neuronal processing differentiating between the two processes occurring deeper in the brain than can be measured by ERPs. Study 2. Extrinsic rewards contingent on memory performance can boost memory and learning. However, the effects of extrinsic rewards on memory specificity, particularly in regards to the process of pattern separation, are not well understood. In this behavioral study, we evaluate how extrinsic rewards affect behavioral performance in a task that taxes pattern separation. Our data show that rewards given for participation at the time of encoding boost mnemonic discrimination between target-lure pairs while rewards given for memory performance at the time of retrieval do not. We hypothesize this is because pattern separation is an encoding dependent process. This boost in discriminability is only seen when the rewarded stimuli are blocked together in separate blocks from the non-rewarded stimuli. When the rewarded and non-rewarded stimuli are interspersed within blocks, discriminability does not significantly differ between the rewarded and non-rewarded trials. Overall, performance was better when rewards were contingent on performance than when rewards independent of performance, although this difference is eliminated when attention during encoding is controlled.

<p>Recurrent stress has been found to impair brain structures essential to memory. The cognitive reserve model suggests that physical activity supplies protection against memory decline in neuropathologies. The purpose of the present study was to explore whether leisure physical activity modifies the predicted negative effect stress has on memory. A sub-sample derived from the Betula Study comprised 267 participants between 50 and 65 years. Memory was assessed by a SPT free recall and stress by a self-report. Low and High frequency exercisers were analyzed separately. After age, sex and education were controlled for in hierarchical regression, results showed that stress significantly improved memory performance in Low exercisers but no significant effect in High exercisers. Thus, frequency of physical activity did not explain variation in memory performance. However, higher age did not have a negative influence on memory performance for the High exercisers.</p>

<p>Verbal information has predominantly been the to-be-remembered materials in human memory research for more than a century. In recent years some interesting deviations from the established rules of verbal memory have been observed in subjects who have been asked to motorically self-perform (enact) action sentences at the encoding phase of the memory task, instead of only hearing or reading them as in a traditional verbal task (VT). Marked enhancements in recall were also consistently demonstrated in such studies and the effect was named the subject-performed task (SPT) effect. Presently, the body of SPT research is large but little agreement has been reached regarding the mechanism at work in producing the SPT phenomenon. The present thesis addresses two major issues in SPT research. The enhancement of associative information and the significance of the motor component are evaluated. In Study A, the SPT effect was studied in two cued-recall tasks that relied on item-specific association and relational association, respectively. The results showed that SPT encoding interacts with item-specific associative cues at recall to produce a larger SPT effect as compared to free recall. This supports the notion that part of the SPT effect is due to enhanced item-specific association. In Study B, the associative effect in SPT was studied amongst age cohorts comprised of subjects between 40 and 85 years old. Normal age-related decline in episodic memory has elsewhere been suggested to be caused mainly by associative deficits connected with ageing. The results of Study B indicate that the item-specific associative effect in SPT was more age sensitive than recall of VT and the relational associative effect in SPT. In Study C, the question over whether the SPT effect is dependent on motor modality or not was addressed. Self-produced sign language encoding was argued to be qualitatively the same as self-produced oral/verbal encoding, with the motor modality component being the only exception. It was also argued that the motor modality component was the main similarity to performing SPT. Since the signing subjects performed at the same level as the SPT condition at recall, and better than the control conditions (e.g., VT), the conclusion was made that motor activation per se can contribute to memory enhancement in SPT. Whether SPT encoding results in qualitatively different memory traces is discussed as well as the effect of SPT on other types of associative information. The results are also briefly related to other controversies in SPT research. It is concluded, finally, that enactment produces differential effects on different types of associations. The association between verb and noun is clearly enhanced by SPT encoding. Moreover, it is concluded that overt motor activation is necessary for obtaining a full SPT effect. To explore these interactions further and to build upon these conclusions, an increased focus on motor processes and their relation to verbal processes is called for in future cognitive research.</p>

<p>Research on children with Attention Deficit Hyperactivity Disorder (ADHD) has shown that they are extremely sensitive to distraction from external stimuli that lead to poor cognitive performance. This thesis shows that cognitive performance can be improved if this external stimulus is smooth and continuous (e.g. auditory white noise). Control children attenuate their performance under such conditions. The first Study proposes the moderate brain arousal model (MBA). This neurocomputational model predicts selective improvement from noise in ADHD children. Noise through a phenomenon called stochastic resonance (SR), can be beneficial in dopamine deprived neural systems. The statistical phenomenon of SR explains how the signal-to-noise ratio can be improved by noise in neural systems where the passing a threshold is required. The second Study provides experimental support for the MBA-model by showing that ADHD children improve performance in a free recall task while exposed to auditive noise. Control children declines in the same condition. The third Study generalizes this finding among low achieving children, which it is argued have low dopamine levels. Noise exposure improves performance in low achievers, but inhibits performance in high achievers. The conclusion is that external auditory noise can restore low dopamine levels and thus improve cognitive performance. It is also proposed that dopamine levels modulate the SR effect; this means that low dopamine persons require more noise to obtain an SR effect. Both excessive and insufficient dopamine is detrimental for cognitive performance. The MBA model can be used to explain several shortcomings where changes in the dopamine system have been identified. The MBA model can also help create appropriate and adaptive environments, especially in schools, for persons with a deficient dopamine function, such as ADHD children.</p>